Q8CJG0 · AGO2_MOUSE

  • Protein
    Protein argonaute-2
  • Gene
    Ago2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Required for RNA-mediated gene silencing (RNAi) by the RNA-induced silencing complex (RISC). The 'minimal RISC' appears to include AGO2 bound to a short guide RNA such as a microRNA (miRNA) or short interfering RNA (siRNA). These guide RNAs direct RISC to complementary mRNAs that are targets for RISC-mediated gene silencing. The precise mechanism of gene silencing depends on the degree of complementarity between the miRNA or siRNA and its target. Binding of RISC to a perfectly complementary mRNA generally results in silencing due to endonucleolytic cleavage of the mRNA specifically by AGO2. Binding of RISC to a partially complementary mRNA results in silencing through inhibition of translation, and this is independent of endonuclease activity. May inhibit translation initiation by binding to the 7-methylguanosine cap, thereby preventing the recruitment of the translation initiation factor eIF4-E. May also inhibit translation initiation via interaction with EIF6, which itself binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit. The inhibition of translational initiation leads to the accumulation of the affected mRNA in cytoplasmic processing bodies (P-bodies), where mRNA degradation may subsequently occur. In some cases RISC-mediated translational repression is also observed for miRNAs that perfectly match the 3' untranslated region (3'-UTR). Can also up-regulate the translation of specific mRNAs under certain growth conditions. Binds to the AU element of the 3'-UTR of the TNF (TNF-alpha) mRNA and up-regulates translation under conditions of serum starvation. Also required for transcriptional gene silencing (TGS), in which short RNAs known as antigene RNAs or agRNAs direct the transcriptional repression of complementary promoter regions. Regulates lymphoid and erythroid development and function, and this is independent of endonuclease activity.

Catalytic activity

  • Endonucleolytic cleavage to 5'-phosphomonoester.
    EC:3.1.26.n2 (UniProtKB | ENZYME | Rhea)

Cofactor

Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

Mn2+ (UniProtKB | Rhea| CHEBI:29035 )

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site598a divalent metal cation (UniProtKB | ChEBI)
Binding site670a divalent metal cation (UniProtKB | ChEBI)
Binding site808a divalent metal cation (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentchromatoid body
Cellular Componentcytoplasm
Cellular Componentcytoplasmic ribonucleoprotein granule
Cellular Componentcytoplasmic stress granule
Cellular Componentcytosol
Cellular Componentdendrite
Cellular Componentextracellular exosome
Cellular ComponentGolgi apparatus
Cellular Componentmembrane
Cellular Componentmitochondrion
Cellular Componentnucleus
Cellular ComponentP granule
Cellular ComponentP-body
Cellular Componentpi-body
Cellular Componentribonucleoprotein complex
Cellular ComponentRISC complex
Cellular ComponentRISC-loading complex
Molecular Functioncore promoter sequence-specific DNA binding
Molecular Functiondouble-stranded RNA binding
Molecular Functionendoribonuclease activity, cleaving miRNA-paired mRNA
Molecular Functionendoribonuclease activity, cleaving siRNA-paired mRNA
Molecular FunctionHsp70 protein binding
Molecular FunctionHsp90 protein binding
Molecular Functionmetal ion binding
Molecular FunctionmiRNA binding
Molecular FunctionmRNA 3'-UTR AU-rich region binding
Molecular FunctionmRNA binding
Molecular FunctionmRNA cap binding
Molecular FunctionRISC complex binding
Molecular FunctionRNA 7-methylguanosine cap binding
Molecular FunctionRNA binding
Molecular FunctionRNA endonuclease activity
Molecular FunctionRNA polymerase II complex binding
Molecular Functionsingle-stranded RNA binding
Molecular FunctionsiRNA binding
Biological Processcell differentiation
Biological ProcessmiRNA metabolic process
Biological ProcessmiRNA processing
Biological ProcessmiRNA-mediated gene silencing by inhibition of translation
Biological ProcessmiRNA-mediated gene silencing by mRNA destabilization
Biological Processnegative regulation of amyloid precursor protein biosynthetic process
Biological Processnegative regulation of translational initiation
Biological Processpositive regulation of angiogenesis
Biological Processpositive regulation of gene expression
Biological Processpositive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay
Biological Processpositive regulation of nuclear-transcribed mRNA poly(A) tail shortening
Biological Processpositive regulation of post-transcriptional gene silencing by RNA
Biological Processpositive regulation of transcription by RNA polymerase II
Biological Processpositive regulation of translation
Biological Processpositive regulation of trophoblast cell migration
Biological Processpost-embryonic development
Biological Processpre-miRNA processing
Biological Processregulation of mRNA stability
Biological Processregulatory ncRNA-mediated gene silencing
Biological Processregulatory ncRNA-mediated post-transcriptional gene silencing
Biological ProcessRISC complex assembly
Biological ProcessRNA secondary structure unwinding
Biological ProcesssiRNA processing
Biological ProcesssiRNA-mediated gene silencing by mRNA destabilization

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Protein argonaute-2
  • EC number
  • Short names
    Argonaute2
    ; mAgo2
  • Alternative names
    • Argonaute RISC catalytic component 2
    • Eukaryotic translation initiation factor 2C 2
      (eIF-2C 2
      ; eIF2C 2
      )
    • Piwi/argonaute family protein meIF2C2
    • Protein slicer

Gene names

    • Name
      Ago2
    • Synonyms
      Eif2c2, Kiaa4215

Organism names

  • Taxonomic identifier
  • Strain
    • B5/EGFP
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q8CJG0
  • Secondary accessions
    • A1A563
    • Q4VAB3
    • Q571J6

Proteomes

Organism-specific databases

Subcellular Location

Keywords

Phenotypes & Variants

Disruption phenotype

Embryonic death with a strong defect in neural tube closure and apparent cardiac failure.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 45 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00001940581-860Protein argonaute-2
Modified residue23'-nitrotyrosine
Modified residue388Phosphoserine
Modified residue7014-hydroxyproline
Modified residue825Phosphoserine
Modified residue829Phosphoserine
Modified residue832Phosphoserine
Modified residue835Phosphoserine

Post-translational modification

Hydroxylated. 4-hydroxylation appears to enhance protein stability but is not required for miRNA-binding or endonuclease activity.
Ubiquitinated on surface-exposed lysines by a SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 during target-directed microRNA degradation (TDMD), a process that mediates degradation of microRNAs (miRNAs). Ubiquitination by the SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 leads to its subsequent degradation, thereby exposing miRNAs for degradation. ZSWIM8 recognizes and binds AGO2 when it is engaged with a TDMD target.
Phosphorylation at Ser-388 by AKT3; leads to up-regulate translational repression of microRNA target and down-regulate endonucleolytic cleavage.
A phosphorylation cycle of C-terminal serine cluster (Ser-825-Ser-835) regulates the release of target mRNAs. Target-binding leads to phosphorylation of these residues by CSNK1A1, which reduces the affinity of AGO2 for mRNA and enables target release. The ANKRD52-PPP6C phosphatase complex dephosphorylates the residues, which primes AGO2 for binding a new target.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Ubiquitous expression in 9.5 day embryos with highest levels in forebrain, heart, limb buds, and branchial arches.

Gene expression databases

Interaction

Subunit

Interacts with DICER1 through its Piwi domain and with TARBP2 during assembly of the RNA-induced silencing complex (RISC). Together, DICER1, AGO2 and TARBP2 constitute the trimeric RISC loading complex (RLC), or micro-RNA (miRNA) loading complex (miRLC). Within the RLC/miRLC, DICER1 and TARBP2 are required to process precursor miRNAs (pre-miRNAs) to mature miRNAs and then load them onto AGO2. AGO2 bound to the mature miRNA constitutes the minimal RISC and may subsequently dissociate from DICER1 and TARBP2. Note however that the term RISC has also been used to describe the trimeric RLC/miRLC. The formation of RISC complexes containing siRNAs rather than miRNAs appears to occur independently of DICER1 (PubMed:16357216).
Interacts with AGO1. Also interacts with DDB1, DDX5, DDX6, DDX20, DHX30, DHX36, DDX47, DHX9, ELAVL, FXR1, GEMIN4, HNRNPF, IGF2BP1, ILF3, IMP8, MATR3, PABPC1, PRMT5, P4HA1, P4HB, RBM4, SART3, TNRC6A, TNRC6B, UPF1 and YBX1. Interacts with the P-body components DCP1A and XRN1. Associates with polysomes and messenger ribonucleoproteins (mNRPs). Interacts with RBM4; the interaction is modulated under stress-induced conditions, occurs under both cell proliferation and differentiation conditions and in an RNA- and phosphorylation-independent manner. Interacts with LIMD1, WTIP and AJUBA (By similarity).
Interacts with TRIM71 (PubMed:19898466, PubMed:22508726, PubMed:22735451).
Interacts with APOBEC3G in an RNA-dependent manner. Interacts with APOBEC3A, APOBEC3C, APOBEC3F and APOBEC3H. Interacts with DICER1, TARBP2, EIF6, MOV10 and RPL7A (60S ribosome subunit); they form a large RNA-induced silencing complex (RISC). Interacts with FMR1. Interacts with ZFP36 (By similarity).
Interacts with RC3H1; the interaction is RNA independent (PubMed:25697406).
Interacts with ARB2A (PubMed:29311329).
Found in a complex composed of AGO2, CHD7 and ARB2A (PubMed:29311329).
Interacts with SND1 and SYT11 (PubMed:24882364).
Interacts with CLNK (PubMed:26009488).
Interacts with GARRE1 (By similarity).
Interacts with GRB2; this interaction is important for the formation of a ternary complex containing GRB2, AGO2 and DICER1 (By similarity).

Binary interactions

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for domain, region.

TypeIDPosition(s)Description
Domain230-349PAZ
Region312-317Interaction with guide RNA
Domain518-819Piwi
Region525-567Interaction with guide RNA
Region588-591Interaction with GW182 family members
Region651-661Interaction with GW182 family members
Region710-711Interaction with guide RNA
Region754-762Interaction with guide RNA
Region791-813Interaction with guide RNA

Domain

The Piwi domain may perform RNA cleavage by a mechanism similar to that of RNase H. However, while RNase H utilizes a triad of Asp-Asp-Glu (DDE) for metal ion coordination, this protein appears to utilize a triad of Asp-Asp-His (DDH).

Sequence similarities

Belongs to the argonaute family. Ago subfamily.

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    860
  • Mass (Da)
    97,304
  • Last updated
    2011-07-27 v3
  • Checksum
    A4E13C633846062C
MYSGAGPVLASPAPTTSPIPGYAFKPPPRPDFGTTGRTIKLQANFFEMDIPKIDIYHYELDIKPEKCPRRVNREIVEHMVQHFKTQIFGDRKPVFDGRKNLYTAMPLPIGRDKVELEVTLPGEGKDRIFKVSIKWVSCVSLQALHDALSGRLPSVPFETIQALDVVMRHLPSMRYTPVGRSFFTASEGCSNPLGGGREVWFGFHQSVRPSLWKMMLNIDVSATAFYKAQPVIEFVCEVLDFKSIEEQQKPLTDSQRVKFTKEIKGLKVEITHCGQMKRKYRVCNVTRRPASHQTFPLQQESGQTVECTVAQYFKDRHKLVLRYPHLPCLQVGQEQKHTYLPLEVCNIVAGQRCIKKLTDNQTSTMIRATARSAPDRQEEISKLMRSASFNTDPYVREFGIMVKDEMTDVTGRVLQPPSILYGGRNKAIATPVQGVWDMRNKQFHTGIEIKVWAIACFAPQRQCTEVHLKSFTEQLRKISRDAGMPIQGQPCFCKYAQGADSVEPMFRHLKNTYAGLQLVVVILPGKTPVYAEVKRVGDTVLGMATQCVQMKNVQRTTPQTLSNLCLKINVKLGGVNNILLPQGRPPVFQQPVIFLGADVTHPPAGDGKKPSIAAVVGSMDAHPNRYCATVRVQQHRQEIIQDLAAMVRELLIQFYKSTRFKPTRIIFYRDGVSEGQFQQVLHHELLAIREACIKLEKDYQPGITFIVVQKRHHTRLFCTDKNERVGKSGNIPAGTTVDTKITHPTEFDFYLCSHAGIQGTSRPSHYHVLWDDNRFSSDELQILTYQLCHTYVRCTRSVSIPAPAYYAHLVAFRARYHLVDKEHDSAEGSHTSGQSNGRDHQALAKAVQVHQDTLRTMYFA

Sequence caution

The sequence AAH96465.1 differs from that shown. Reason: Erroneous initiation Extended N-terminus.

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict65in Ref. 2; AAH96465
Sequence conflict67in Ref. 1; BAC15767
Sequence conflict129in Ref. 1; BAC15767
Sequence conflict360in Ref. 1; BAC15767
Sequence conflict563in Ref. 2; AAH96465
Sequence conflict711in Ref. 2; AAH96465
Sequence conflict761in Ref. 1; BAC15767

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AB081472
EMBL· GenBank· DDBJ
BAC15767.1
EMBL· GenBank· DDBJ
mRNA
BC096465
EMBL· GenBank· DDBJ
AAH96465.1
EMBL· GenBank· DDBJ
mRNA Different initiation
BC128379
EMBL· GenBank· DDBJ
AAI28380.1
EMBL· GenBank· DDBJ
mRNA
BC129922
EMBL· GenBank· DDBJ
AAI29923.1
EMBL· GenBank· DDBJ
mRNA
AK220193
EMBL· GenBank· DDBJ
BAD90378.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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